This revised multi-center proposal takes advantage of the existing Studies in Pediatric Liver Transplant (SPLIT) registry augmented by additional prospectively-obtained data to test an objective measure of adherence to immunosuppressant medications in children who had a liver transplant. Nonadherence is the most important reason for organ rejection in long term survivors of pediatric liver transplantation. In order to address this important risk-factor effectively, the first step is to evaluate a method that would identify nonadherence in these children. Medication blood levels that are obtained as a part of clinical practice in transplant centers can be used to determine whether the patient is adherent or not. Calculating the degree of fluctuation of medication blood levels over time for each patient would identify nonadherence (more fluctuation = less consistent medication-taking = less adherence). The degree of fluctuation in medication blood levels is correlated with rejection episodes. This grant evaluates the use of this method (calculating the variability in medication blood levels) along with other ancillary measures of adherence in a large group of transplant patients. It determines a threshold of adherence (when does nonadherence begin to be associated with organ rejection). This proposal also takes advantage of the prospectively-followed cohort to evaluate psychosocial predictors for nonadherence. Those predictors can be used to inform intervention efforts to improve adherence. Since this proposal will validate a clinically- useful method to assess adherence, the results are expected to enhance survival and reduce rejections in pediatric transplant recipients. Results are also expected to inform adherence research in other fields: the novel, objective, biological marker for nonadherence can be used in other populations. Furthermore, the detection method will provide the essential basis to support adherence research in the transplant setting (such as treatment strategies), results from which can be generalized to other settings. PUBLIC HEALTH RELEVANCE: The survival of children who have received an organ transplant is dependent on immunosuppressant medications, but many stop taking them. This proposal will validate a method to identify children who are at risk because of not taking their medications. The results will help transplant centers identify these children and improve overall post transplant survival, and will also inform other areas of medicine in which children may not take their medications as prescribed.